TRILACICLIB IMPROVES OVERALL SURVIVAL WHEN GIVEN WITH / (GCb) IN PATIENTS WITH METASTATIC TRIPLE NEGATIVE (mTNBC) IN A RANDOMIZED, OPEN-LABEL, PHASE 2 TRIAL

Joyce O’Shaughnessy1, Gail S. Wright2, Anu R. Thummala3, Michael A. Danso4, Lazar Popovic5, Timothy J. Pluard6, Hyo Sook Han7, Zeljko Vojnovic8, Nikola Vasev9, Ling Ma10, Donald A. Richards11, Sharon T. Wilks12, Dušan Milenković13, Jessica A. Sorrentino14, Zhao Yang14, Janet K. Horton14, Antoinette R. Tan15

Baylor University Medical Center, Texas Oncology Dallas, US Oncology Research1, Florida Cancer Specialists (North)2, Comprehensive Cancer Centers of Nevada, US Oncology Research3, Virginia Oncology Specialists, US Oncology Research4,Oncology Institute of Vojvodina, University of Novi Sad5, Saint Luke’s Cancer Institute6, Moffitt Cancer Center7, County Hospital Varazdin8, University Clinic of Radiotherapy and Oncology9, Rocky Mountain Cancer Centers, US Oncology Research10, Texas Oncology Tyler, US Oncology Research11, Texas Oncology San Antonio Northeast, US Oncology Research12, Clinical Center Niš13, G1 Therapeutics14, Levine Cancer Institute, Atrium Health15 esmo.org DISCLOSURES Joyce O’Shaughnessy, MD

Personal consultation fees: AbbVie Inc., Agendia, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene Corporation, Eisai, G1 Therapeutics Inc., Genentech, Genomic Health, GRAIL, Immunomedics, Heron Therapeutics, Ipsen , Jounce Therapeutics, Lilly, Merck, Myriad, Novartis, Ondonate Therapeutics, , Puma Biotechnology, Prime Oncology, Roche, Seattle Genetics, and Syndax Pharmaceuticals

Study sponsored by G1 Therapeutics, Inc. (G1T28), A HIGHLY POTENT, TRANSIENT CDK 4/6 INHIBITOR, HAS THE POTENTIAL TO DECREASE MYELOTOXICITY AND IMPROVE ANTI-TUMOR EFFICACY

 Gemcitabine + carboplatin (GCb) causes treatment- Preserves immune cell function and limiting cumulative myelosuppression1 potentially directly enhances immune response Normal A. Alters the proliferation kinetics and composition of compromising anti-tumor efficacy Cell intratumor T-cell subsets to favor increased effector T cell function  -induced immune cell toxicity may limit B. Enhances T-cell activation 2,3 C. Increases antigen processing and presentation on tumor host immune system’s response against TNBC Trilaciclib cells (CDK4/6 inhibitor) Tumor D. Reduces immunosuppressive function of regulatory cells

 Trilaciclib is an IV CDK4/6 inhibitor, which can induce M G2 transient G1 arrest in immune cells and HSPCs, S potentially preserving T-cell function and bone marrow G1 Proactive protection of HSPC prevents

arrest during chemotherapy during arrest chemotherapy-induced myelosuppression 1 4  Tmax:~0.25–0.5 hr Neutrophil A. Reduces occurrence and duration of Erythrocyte severe neutropenia

4 G Transient  Terminal t1/2: ~14 hr Platelets B. Reduces anemia and thrombocytopenia HSPC C. Reduces need for supportive care  In kinase screen, IC for CDK4/cyclin D1 and T lymphocyte (growth factors, transfusions, 50 chemotherapy dose reductions) B lymphocyte CDK6/cyclin D3 was 1 nmol/L and 4 nmol/L, D. Preserves lymphocytes respectively5

1. O'Shaughnessy J, et al. J Clin Oncol. 2014;32:3840–7; 2. Lyman GH. Oncology (Williston Park). 2006;20:16–25; 3. Smith RE. J Natl Compr Canc Netw. 2006;4:649–58; 4. He S, et al. Sci Transl Med. 2017;9:pii:eaal3986; 5. Bisi JE, et al. Mol Cancer Ther. 2016;15:783–93. CDK, cyclin-dependent kinase; GCb, gemcitabine/carboplatin; hr, hour(s); HSPC, hematopoietic stem and progenitor cell; IC50, half maximal inhibitory concentration; IV, intravenous; mTNBC, metastatic triple-negative breast cancer; t1/2, half-life; Tmax, time when maximum plasma concentration is reached. RANDOMIZED, OPEN-LABEL, MULTICENTER, GLOBAL PHASE 2 STUDY OF TRILACICLIB PLUS GCb IN PATIENTS WITH mTNBC (G1T28-04; NCT02978716)

Treatment was given in 21-day cyclesb Cycle 1 Cycle 1 Cycle 1 Cycle 1

a Day 1 Day 2 Day 8 Day 9 Group 1 GCb GCb n=34 Patients were Survival Group 2 GCb + GCb + treated until PD or

1:1:1 follow-up N=102 N=142 n=33 Trilaciclib Trilaciclib unacceptable Screening toxicity Group 3 GCb + GCb + Trilaciclib Trilaciclib n=35 Trilaciclib Trilaciclib Randomization by by IWRS Randomization Gemcitabine was administered at 1000 mg/m2 and carboplatin at AUC2 Trilaciclib 240 mg/m2 was administered IV over 30 (±5) minutes prior to GCb Eligibility criteria

 Evaluable, locally recurrent or metastatic TNBC

 TNBC defined as ER and PR negative (local assessment of IHC; <10% nuclei staining) and HER2- per ASCO CAP 9 9  Hemoglobin ≥9.0 g/dL; ANC ≥1·5 ×10 /L; platelets ≥100 ×10 /L

 0–2 prior cytotoxic regimens for locally recurrent/metastatic disease

 ECOG PS 0─1 a Randomization stratified by number of prior lines of systemic therapy (0 vs 1 or 2) and presence of liver metastases (Yes or No). b CBCs assessed minimum of at least once per week during each chemotherapy cycle; FACT-An and FACT-B administered on Day 1 of each Cycle in the treatment phase and at the post treatment visit; prophylactic growth factors were not allowed in Cycle 1, otherwise, supportive care was allowed as needed. ASCO CAP, American Society of Clinical Oncology College of American Pathologists; CBC, complete blood count; ECOG PS, Eastern Cooperative Oncology Group performance status; ER, estrogen receptor; FACT-AN, Functional Assessment of Cancer Therapy-Anemia; FACT-B, FACT-Breast Cancer; GCb, gemcitabine/carboplatin; HER2-, human epidermal growth factor receptor 2 negative; IHC, immunohistochemistry; IV, intravenously; IWRS, interactive web-response system; mTNBC, metastatic triple-negative breast cancer; PD, progressive disease; PR, progesterone receptor. ENDPOINTS AND STATISTICAL ANALYSES

 Analyses of endpoints were prespecified to demonstrate superiority of Myelosuppression efficacy endpoints Group 3 over Group 1 for at least one primary endpoint Primary Duration of severe (G4) neutropenia in Cycle 1  With 102 pts, the study would have 90% power to detect the treatment Occurrence of severe (G4) neutropenia during treatment period effect specified below at a 2-sided significance level of 0.05

Key secondarya Occurrence of RBC transfusions  3-day reduction of duration of severe neutropenia (DSN) in

Occurrence of G-CSF administrations Cycle 1, or

Occurrence of platelet transfusions  41% absolute reduction in the proportion of patients with SN

Antitumor efficacy endpoints  Group 2 vs Group 1 and Groups 2 + 3 vs Group 1 were prespecified secondary comparisons Secondary ORR

 PFS Timing of the PFS and OS analyses was determined by an independent DMC who viewed PFS/OS as a safety endpoint OS  PFS and OS median times and HRs calculated with 95% CIs and TEAEs and additional safety endpoints nominal p values

Exploratory endpoints  OS is planned to be final when ≥ 70% events have occurred PROs  Median follow-up for all patients: 10.5 months (range: 0.1–25.8 months)

a Key secondary endpoints assessed throughout treatment period; occurrence of RBC transfusions determined on/after Week 5. DMC, data monitoring committee; DSN, duration of severe neutropenia; G4, Grade 4; G-CSF, granulocyte-colony stimulating factor; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PROs, patient-reported outcomes; RBC, red blood cell; SN, severe neutropenia; TEAEs, treatment-emergent adverse events. BASELINE DEMOGRAPHICS AND TUMOR CHARACTERISTICS Group 1: GCb Group 2: GCb + Group 3: GCb + Total (Day 1/8) Trilaciclib (Day Trilaciclib (n=102) (n=34) 1/8) (n=33) (Day 1/2/8/9) (n=35) Age, n (%) 18–<65 26 (76.5) 24 (72.7) 26 (74.3) 76 (74.5) ≥65 8 (23.5) 9 (27.3) 9 (25.7) 26 (25.5) Hormone receptors n (%) ER <1% 31 (91.2) 30 (90.9) 33 (94.3) 94 (92.2) ER 1–10% 2 (5.9) 2 (6.1) 2 (5.7) 6 (5.9) ER negative othera 1 (2.9) 1 (3.0) 0 2 (2.0)

PR <1% 29 (85.3) 29 (87.9) 34 (97.1) 92 (90.2) PR 1–10% 4 (11.8) 3 (9.1) 1 (2.9) 8 (7.8) a PR negative, other 1 (2.9) 1 (3.0) 0 2 (2.0) ECOG PS, n (%) 0 15 (44.1) 17 (51.5) 21 (60.0) 53 (52.0) 1 19 (55.9) 16 (48.5) 14 (40.0) 49 (48.0)

a b Indicates patients were defined as TNBC by Liver involvement , n (%) 8 (23.5) 8 (24.2) 10 (28.6) 26 (25.5) investigator; however, pathology reports were not available for confirmation (by Sponsor). Prior cytotoxic regimensb, n (%) b Randomization stratified by number of prior lines of systemic therapy and presence of liver 0 21 (61.8) 22 (66.7) 21 (60.0) 64 (62.7) metastases. ECOG PS, Eastern Cooperative Oncology Group 1 or 2 13 (38.2) 11 (33.3) 14 (40.0) 38 (37.3) performance status; GCb, gemcitabine/carboplatin; TNBC, triple-negative breast cancer. TRILACICLIB INCREASED THE DURATION OF EXPOSURE AND CUMULATIVE DOSES OF GCb COMPARED WITH GCb ALONE

Group 1 GCb Group 2 GCb + Group 3 GCb + (Day 1/8) Trilaciclib (Day 1/8) Trilaciclib (Day 1/2/8/9) (n=30) (n=33) (n=35) Duration of exposure Months, median (min, max) 3.3 (0.7, 14) 5.3 (1.4, 19.6) 5.5 (0.7, 14.3) Cycles, median (min, max) 4 (1, 18) 7 (2, 27) 8 (1, 20) Cumulative dose 7306.2 12000.0 11800.1 Median gemcitabine dose, mg/m2 (min, max) (1000.0, 34396.0) (3000.0, 43565.8) (2000.0, 37004.9) Median carboplatin dose, AUC (min, max) 15.0 (2, 68.5) 24.0 (6, 89) 22.0 (4, 74)

Safety analysis set, based on data cut-off of May 17, 2019. AUC, area under the curve; GCb, gemcitabine/carboplatin. TRILACICLIB PLUS GCb DID NOT SIGNIFICANTLY IMPROVE PRIMARY MYELOSUPPRESSION ENDPOINTS OF DURATION AND OCCURRENCE OF SEVERE (GRADE 4) NEUTROPENIA

Mean duration (days) of severe (G4) 1 2 p‡=0.70 Primary endpoints neutropenia in Cycle 1 1 % of patients with severe (G4) neutropenia during 26.5 36.4 p‡=0.70 treatment period 22.9

Neutrophils 47.1 % of patients with G-CSF administration 63.6 p‡=0.14 40 14.1 All-cause dose reduction rate (n per 100 cycles) 11.8 p‡=0.98 13.3 GCb dose* GCb 35.3 % of patients with RBC transfusion ≥ Week 5 33.3 p‡=0.075 22.9

RBCs 4.6 RBC transfusion rate ≥ Week 5 (n per 100 weeks) 1.9 p‡=0.020 1.6 11.8 % of patients with platelet transfusion 9.1 p‡=0.98 17.1 1.9

Platelets Platelet transfusion rate, n per 100 weeks 0.4 p‡=0.61 1.2 0 10 20 30 40 50 60 70

Group 1: GCb (Day 1/8) (n=34) Group 2: GCb + Trilaciclib (Day 1/8) (n=33) Group 3: GCb + Trilaciclib (Day 1/2/8/9) (n=35)

Based on data as of July 30, 2018. *No dose modifications of trilaciclib were allowed; ‡For comparison between Groups 3 and 1. p-value reported for primary endpoints are multiplicity adjusted one-sided p value, all other p values are two-sided. GCb, gemcitabine/carboplatin; G4, Grade 4; G-CSF, granulocyte-colony stimulating factor; RBC, red blood cell. TRILACICLIB PLUS GCb: KEY ADVERSE EVENTS

Key TEAEs (all Grades) Group 1: GCb Group 2: GCb Group 3: GCb Hematologic AEs Group 1: GCb Group 2: GCb Group 3: GCb reported in ≥20% of (Day 1/8) + Trilaciclib + Trilaciclib (Grade 3/4), n (%) (Day 1/8) + Trilaciclib + Trilaciclib patients in any (n=30) (Day 1/8) (n=33) (Day 1/2/8/9) (n=30) (Day 1/8) (Day 1/2/8/9) treatment group, n (%) (n=35) (n=33) (n=35) Anemia 22 (73.3) 17 (51.5) 15 (42.9) Neutropenia 20 (66.7) 26 (78.8) 20 (57.1) Neutropenia 21 (70.0) 27 (81.8) 23 (65.7) Thrombocytopenia 15 (50.0) 9 (27.3) 15 (42.9) Thrombocytopenia 18 (60.0) 18 (54.5) 22 (62.9) Anemia 14 (46.7) 8 (24.2) 11 (31.4) Fatigue 11 (36.7) 14 (42.4) 15 (42.9) Vomiting 8 (26.7) 7 (21.2) 11 (31.4) Nausea 7 (23.3) 14 (42.4) 17 (48.6) Headache 6 (20.0) 9 (27.3) 14 (40.0)

 Despite more GCb delivered in Groups 2 + 3, hematologic toxicity was similar between groups

 No serious TEAEs, or TEAEs leading to treatment discontinuation, were considered related to trilaciclib

 Trilaciclib TEAEs of special interest were primarily low grade and included headache, injection-site reactions and localized phlebitis

Safety analysis set, based on data cut-off of May 17, 2019; ordered from highest frequency to lowest frequency in Group 1. AEs, adverse events; GCb, gemcitabine/carboplatin; TEAE, treatment-emergent adverse event. TRILACICLIB DID NOT ADVERSELY AFFECT PATIENTS’ OVERALL FUNCTION

Group 2 vs Group 1 Group 3 vs Group 1

Domain No. of Median TTD, Hazard Ratio [95% CI] Domain No. of Median TTD, Hazard Ratio [95% CI] Events Months Events Months Trilaciclib/ Trilaciclib/ Trilaciclib/ Trilaciclib/ GCb only GCb only GCb only GCb only

FACT-G 14/15 NYR/3.12 0.75 [0.36;1.56] FACT-G 15/15 5.9/3.12 0.55 [0.27;1.14]

FACT-B 13/15 NYR/2.89 0.70 [0.33;1.48] FACT-B 15/15 5.9/2.89 0.56 [0.27;1.16]

FACT-An 16/19 4.93/1.48 0.52 [0.26;1.04] FACT-An 18/19 3.52/1.48 0.46[0.24;0.91]

Fatigue 18/21 2.33/1.45 0.58 [0.30;1.11] Fatigue 19/21 3.48/1.45 0.48 [0.25;0.93]

Anemia 17/18 3.98/1.45 0.59 [0.30;1.17] Anemia 20/18 3.52/1.45 0.48 [0.24;0.93] TOI TOI

0.4 0.6 0.8 1 1.67 2.5 0.4 0.6 0.8 1 1.67 2.5 Trilaciclib D1/8 better GCb-only better Trilaciclib D1/2/8/9 better GCb-only better

No worsening of patients’ overall function or QoL with the addition of trilaciclib to GCb

Group 1: GCb (Day 1/8) (n=34); Group 2: GCb + Trilaciclib (Day 1/8) (n=33); Group 3: GCb + Trilaciclib (Day 1/2/8/9) (n=35). Threshold=3 for Fatigue, =8 for FACT-B total, =6 for Anemia TOI, =7 for FACT-G total and FACT-An total, =1 for items. CI, confidence interval; FACT-An, Functional Assessment of Cancer Therapy-Anemia; FACT-G, FACT-General; FACT-B, FACT-Breast; GCb, gemcitabine/carboplatin; NYR, not yet reached; QoL, quality of life; TOI, Trial Outcome Index; ANTITUMOR EFFICACY WITH TRILACICLIB PLUS GCb COMPARED WITH GCb ALONE

Group 2: Group 3: Group 1: GCb + Trilaciclib GCb + Trilaciclib GCb (Day 1/8) (Day 1/8) (Day 1/2/8/9) Best overall response, n (%) (n=24) (n=30) (n=30) ORRa 8 (33.3) 15 (50.0) 11 (36.7) CBR for 24 weeksa,b 9 (37.5) 17 (56.7) 13 (43.3) p-valuec 0.23 0.68

 No significant differences in ORR or CBR between Group 2 vs Group 1 and Group 3 vs Group 1

a Patients were evaluable for response if they had measurable disease at baseline and ≥1 post baseline tumor assessment, investigator-noted clinical progression before the first post baseline tumor scan, or had died due to disease progression before the first post baseline tumor scan. b Per protocol, clinical benefit was determined in response evaluable patients and included any patient who had a complete or partial response at any time post treatment or stable disease for ≥24 weeks. c The two-sided p-value was calculated using stratified exact Cochran-Mantel-Haenszel method to account for the stratification factors. CBR, clinical benefit rate; ORR, overall response rate. PROGRESSION-FREE SURVIVAL (PFS) WITH TRILACICLIB PLUS GCb COMPARED WITH GCb ALONE

1.0 Group 1 (Median=5.7 months) 0.9 Group 2 (Median=9.4 months) 0.8 Group 3 (Median=7.3 months) 0.7 0.6 0.5 0.4

Probability of of PFS Probability 0.3 0.2 0.1 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Months from randomization Patients at risk, n Group 1 34 27 21 19 16 15 11 6 6 5 2 2 2 1 1 0 0 0 0 0 0 0 Group 2 33 30 25 22 20 17 16 13 12 11 8 7 5 4 4 3 2 1 1 1 1 0 Group 3 35 32 29 25 20 18 16 11 9 7 6 5 4 3 2 2 1 1 0 0 0 0 No differences in PFS between Group 3 vs Group 1 (HR=0.59; 95% CI 0.30-1.16; nominal p=0.12); Group 2 vs Group 1 (HR=0.60; 95% CI 0.30-1.18; nominal p=0.13); or Group 2 + 3 vs Group 1 (HR=0.59; 95% CI 0.33-1.05; nominal p=0.063)

Data stable as of May 17, 2019. Group 1: GCb (Day 1/8) (n=34); Group 2: GCb + Trilaciclib (Day 1/8) (n=33); Group 3: GCb + Trilaciclib (Day 1/2/8/9) (n=35). GCb, gemcitabine/carboplatin; HR, hazard ratio; PFS, progression-free survival. OVERALL SURVIVAL (OS) WITH TRILACICLIB PLUS GCb COMPARED WITH GCb ALONE Group 1 Group 2 Group 3 Patients with death, n (%) 20 (58.8) 11 (33.3) 14 (40.0) 1.0 0.9 Median OS, months 12.6 20.1 17.8 0.8 0.7 0.6 0.5 0.4 Group 1 0.3 Group 2

Probability of of being alive Probability 0.2 Group 3 0.1 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 Months from randomization Patients at risk, n Group 1 34 27 27 26 25 23 21 19 18 16 14 13 13 9 6 6 3 2 1 0 0 0 0 0 0 0 0 Group 2 33 33 32 31 28 26 24 22 20 20 19 17 17 15 13 13 12 10 8 5 3 2 1 1 0 0 0 Group 3 35 35 35 35 32 31 30 26 23 21 21 20 19 17 13 13 9 8 5 3 3 1 1 1 1 1 0 OS was longer for Group 3 vs Group 1 (HR=0.34; 95% CI 0.16 – 0.70; nominal p=0.0023), Group 2 vs Group 1 (HR=0.33; 95% CI 0.15-0.74; nominal p=0.028) and Group 2 + 3 vs Group 1 (HR=0.36; 95% CI 0.19-0.67; nominal p=0.0015)

Based on data as of May 17, 2019. Group 1: GCb (Day 1/8) (n=34); Group 2: GCb + Trilaciclib (Day 1/8) (n=33); Group 3: GCb + Trilaciclib (Day 1/2/8/9) (n=35). HR, hazard ratio; OS, overall survival. POOLED OVERALL SURVIVAL (OS) ANALYSIS IN PRESPECIFIED SUBGROUPS Pre-specified subgroup analyses Subgroup No. of patients No. of events HR 95% CI Overall (ITT) 102 (100) 45 0.36 (0·19–0·67) Age <65 years 76 (74·5) 36 0.45 (0·23–0.91) ≥65 years 26 (25·5) 9 0.13 (0·03–0·63) Race White 78 (76·5) 33 0.26 (0·12–0·54) Non-white 24 (23·5) 12 0.92 (0·22–3·84) Liver involvement Yes 26 (25·5) 17 0.33 (0·11–1·01) No 76 (74·5) 28 0.38 (0·18–0·81) Region USA 83 (81·4) 37 0.32 (0·16–0·65) Ex-USA 19 (18·6) 8 0.42 (0·09–2·02) ECOG PS 0 53 (52) 18 0.15 (0·05–0·44) 1 49 (48) 27 0.72 (0·33–1·61) Number of prior lines therapy 0 64 (62·7) 28 0.46 (0·21–0.99) 1 or 2 38 (37·3) 17 0.22 (0·07–0·67) BRCA classification Unknown 66 (64·7) 28 0.42 (0·19–0.92) Positive 8 (7·8) 3 NE (NE–NE) Histological TNBC classification Always 71 (69·6) 31 0.35 (0·17–0·74) Acquired 25 (24·5) 12 0.25 (0·06–1·02)

0.031 0.062 0.125 0.250 0.500 1.00 2.00 4.00

Based on data as of May 17, 2019. Trilaciclib better (Groups 2+3) GCb-only better (Group 1) Group 1: GCb (Day 1/8) (n=34); Group 2: GCb + Trilaciclib (Day 1/8) (n=33); Group 3: GCb + Trilaciclib (Day 1/2/8/9) (n=35). CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; GCb, gemcitabine/carboplatin; HR, hazard ratio; ITT, intention-to-treat; NE, not estimable; TNBC, triple-negative breast cancer. POSSIBLE MECHANISMS OF TRILACICLIB ANTITUMOR EFFICACY

• Increased duration of chemotherapy exposure % IFN-γ-producing CD8+ T cells (IFN-γ+IL-17A-[CD3+CD8+]) • Patients on trilaciclib received ~twice as many 2.5 chemotherapy cycles without increased toxicity Group 1 nor worsening of overall function Group 2 2.0 Group 3 • Protecting and/or enhancing immune cell function,

thereby increasing immune-mediated antitumor effects 1.5 • After ex vivo stimulation, there is a greater number of CD8+ T cells producing IFNγ in 1.0

patients who received GCb + trilaciclib from baseline) (Fold change compared with GCb alone, suggesting a more 2 Log 0.5 functional lymphocyte population • CDK4/6 inhibitors can increase platinum sensitivity and 0 decrease proliferation by inhibiting FOXM1 C1D1 C3D1 C5D1 C7D1 phosphorylation (FOXM1 commonly over-expressed in Patients, n C3D1 C5D1 C7D1 1,2 TNBC) Group 1 13 9 10 Group 2 11 11 8 Group 3 15 10 10 1. Rubio C, et al. Clin Cancer Res. 2019;25:390–402. 2. Ni Y, et al. Nature Comm 2019; 10: 2860. FOXM1, Forkhead Box M1; GCb, gemcitabine/carboplatin; IFNγ, interferon-gamma; IL, interleukin; Rb, retinoblastoma; TNBC, triple-negative breast cancer. CONCLUSIONS

 The addition of trilaciclib to GCb in patients with mTNBC did not improve the primary myelosuppression endpoints of duration of severe neutropenia in cycle 1 and occurrence of severe neutropenia

 There were no significant differences in ORR and PFS with addition of trilaciclib to GCb

 There was a significant improvement in OS with trilaciclib added to GCb with both dosing schedules

 Trilaciclib did not increase high-grade toxicity when added to GCb, despite patients having received more cycles of therapy (median 7 or 8 cycles) compared with GCb alone (median 4 cycles)

 The addition of trilaciclib to GCb did not worsen the patients’ functional status on chemotherapy

 Preliminary evidence suggests trilaciclib may enhance CD8+ T cell activation

 Additional biomarker studies, including PDL1 expression, are ongoing to evaluate potential immune effects of trilaciclib on patients’ outcomes

 Final OS analyses will be performed when ≥70% events have occurred

 Further evaluation of trilaciclib with platinum-based chemotherapy in TNBC is warranted

GCb, gemcitabine/carboplatin; mTNBC, metastatic triple-negative breast cancer; ORR, overall response rate; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival; SN, severe neutropenia. ACKNOWLEDGEMENTS

 We thank and acknowledge all of the patients, their families, and site personnel for participating in the study

 All global investigators for the G1T28-04 Study Group

 Medical writing support was provided by Alligent Europe (Envision Pharma Group), funded by G1 Therapeutics, Inc. Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial Antoinette R Tan, Gail S Wright, Anu R Thummala, Michael A Danso, Lazar Popovic, Timothy J Pluard, Hyo S Han, Željko Vojnović, Nikola Vasev, Ling Ma, Donald A Richards, Sharon T Wilks, Dušan Milenković, Zhao Yang, Joyce M Antal, Shannon R Morris, Joyce O’Shaughnessy

Lancet Oncol 2019; September 28, 2019 http://dx.doi.org/10.1016/S1470-2045(19)30616-3

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